Clonal Hematopoiesis of Indeterminate Potential With Loss of <i>Tet2</i> Enhances Risk for Atrial Fibrillation Through <i>Nlrp3</i> Inflammasome Activation

Abstract

We identified a modest association between CHIP, particularly <i>TET2</i> CHIP, and incident AF in the UK Biobank population. In a mouse model of AF resulting from hematopoietic-specific inactivation of <i>Tet2</i>, we propose altered calcium handling as an arrhythmogenic mechanism, dependent on <i>Nlrp3</i> inflammasome activation. Our data are in keeping with previous studies of CHIP in cardiovascular disease, and further studies into the therapeutic potential of NLRP3 inhibition for individuals with <i>TET2</i> CHIP may be warranted.